The role of protease inhibitor therapy in children with HIV infection

In comparison with HIV infection in adults, higher HIV RNA levels in children with perinatal HIV infection, differences in the natural history of HIV disease progression, and the presence of a relatively immature immune system contribute to the more complex and problematic nature of pediatric antiretroviral therapy. Current US treatment guidelines for pediatric HIV infection advocate aggressive therapy with potent combination antiretroviral regimens, to achieve profound and durable suppression of viral replication and preservation of immune function. The combination of a protease inhibitor (PI) and dual nucleoside reverse transcriptase inhibitors (NRTIs) is the most commonly recommended form of highly active antiretroviral treatment (HAART). However, use of PI therapy in pediatrics has been constrained by the lack of suitable drug formulations, a paucity of pharmacokinetic and safety data, and drug intolerance. Pharmacokinetic studies of PIs demonstrate frequent diffrences between children and adults, and greater variability among children, which has led to subtherapeutic dosage regimens and the development of viral resistance. The optimal dosage of many PIs in younger children is not yet known. A therapeutically important drug interaction associated with PIs is that occurring between the various PIs themselves, which allows lower doses of PI at less frequent intervals. Dual PI regimens will probably become more common, as they permit a simpler antiretroviral regimen, lower pill/medication burden, fewer adverse effects and improved adherence. Poor adherence to antiretroviral therapy remains the greatest barrier to overall success in the treatment of HIV-infected children. The key to improving adherence in HIV-infected children is to find treatment regimens that are better suited to their normal life. With improvements in existing PIs and the development of newer ones, simplification of current antiretroviral therapy to once-daily regimens without loss of potency should be achievable. PI-containing HAART has transformed HIV infection into a chronic illness, and HIV-infected children now live longer.